Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 142, Issue 3, Pages 629-640Publisher
WILEY
DOI: 10.1002/ijc.31071
Keywords
nano-pulse stimulation; tumor ablation; immunogenic cell death; breast cancer; immune response; dendritic cell activation
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Funding
- Start-up fund from Frank Reidy Research Center for Bioelectrics, Old Dominion University
- Pulse Biosciences, Inc.
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Nano-pulse stimulation (NPS) as a developing technology has been studied for minimally invasive, nonthermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1-Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression. All tumor-free mice were protected from secondary tumor cell challenge, demonstrating a vaccine-like effect. NPS treatment induced antitumor immunity, long-term memory T cells, destruction of tumor microenvironment and reversal of the massive increase of immune suppressor cells in the tumor microenvironment and blood. NPS-treated 4T1 cells exhibited release of damage-associated molecular patterns (DAMPs), including calreticulin, HMGB1 and ATP, and activated dendritic cells. Those findings suggest that NPS is a potent immunogenic cell death inducer that elicits antitumor immunity to prevent distant metastases in addition to local tumor eradication.
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